Our team is interested in deciphering pathways associated with a number of rare genetic diseases affecting the skeletal muscle. We are in particular interested in understanding the patho-physiology of FacioScapuloHumeral Dystrophy (FSHD), a peculiar muscular dystrophy linked to subtelomeric imbalance and involving epigenetic processes. FSHD, the third most common myopathy, is transmitted in an autosomal dominant manner and is linked to a subtelomeric alteration. Through strong translational interactions, our work has brought a better understanding of the FSHD locus at the genomic and epigenomic level. We are also studying the role of the chromatin factor SMCHD1 the disease and the involvement of this chromatin-associated factor in epigenetic processes in general. Moreover, the exploration of large cohorts of FSHD patients has allowed us to identify new strategies for the diagnosis of this complex disease and the transfer of diagnostic methods to the hospital or the pursuit of diagnosis when the routine diagnosis is not conclusive.
A second strong focus of our team is based on the production and exploration of patients’ induced pluripotent stem cells (hiPSC) for modeling neuromuscular disorders (such as SMA, DMD or Lama2-CMD). This project led by Dr. Leslie Caron contributes to the identification of novel disease-causing genes for patients in diagnosis deadlock. To this aim, we continuously collaborate with hospital services and gathered large collections of biological samples that can be exploited experimentally. We also developed tools and expertise for the development of hiPSCs-based models for modeling pathologies affecting skeletal muscles and neuromuscular junctions, including tissue bioengineering and bioprinting (project led by Dr. Stefano Testa). By combining state-of-the-art molecular and functional technologies (transcriptomics, multi-omics, NGS, RNAscope, calcium imaging and MEA), we are able to identify the genes, biological pathways and functional properties affected in neuromuscular diseases. Overall, all projects open new avenues for understanding muscle pathologies and will facilitate the development of innovative therapeutic approaches.